Association of Colorectal Cancer Susceptibility Loci Alone and in Combination with Adherence to the WCRF/AICF Guidelines for Cancer Prevention on Colorectal Cancer Risk Open Access

Maillis, Alexander (Spring 2019)

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Background: Colorectal cancer (CRC) is the 3rd most common cancer in men and women combined worldwide. Previous genome-wide association studies (GWAS) identified several common genetic variants associated with CRC risk. Additionally, observational studies demonstrated that healthy lifestyle choices are strongly association with colorectal neoplasms; however, little is known about joint effects of genetics and lifestyle on CRC risk.

Methods: A nested case control study including 1,462 CRC cases and 1,482 controls was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of more than 520,000 participants from 10 Western European countries. Odds ratios and 95% confidence intervals for the risk of CRC by categories of genetic risk score (GRS) alone and in combination with the WCRF/AICR score were estimated from unconditional logistic regression models, with adjustment for age at recruitment, sex, and study center.

Results:  Study participants with ≥18 CRC susceptibility loci had a statistically significantly higher risk for CRC (OR = 1.36; 95%: 1.09, 1.69) when compared to those with <14 loci. A high adherence to the WCRF/AICR recommendations was statistically significantly associated with a lower risk for CRC (OR = 0.79; 95%: 0.63, 0.98) compared to study participants with the least concordance. Joint analysis of the GRS and WCRF/AICR recommendation adherence suggested that better concordance with the WCRF/AICR recommendations is associated with lower CRC risk, regardless of genetic risk, so that individuals with low adherence to the WCRF/AICR recommendations and high genetic risk were at a statistically significantly higher risk of CRC compared to those with low genetic risk and high adherence to the WCRF/AICR recommendations (OR = 1.63; 95%: 1.12, 2.38).

Conclusion: Our study suggests that adherence to the WCRF/AICR recommendations is associated with lower CRC risk regardless of the genetic risk.

Table of Contents

Table of Contents

I.                  Background                                                                               1

a.     Colorectal Cancer Incidence and Mortality

b.     Colorectal Cancer Risk Factors

c.      Colorectal Cancer Screening

d.     Genetic Risk Alleles of Colorectal Cancer

e.      WCRF/AICR Recommendations

f.       Gene-Environment Interaction

II.               Methods                                                                                     11

III.            Results                                                                                         16       

IV.            Discussion                                                                                   18

V.               Future Directions                                                                      21

VI.            Citations                                                                                      22

VII.         Tables                                                                                           26

VIII.      Figures                                                                                         30

IX.            Appendices                                                                                 31

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